The major goal of this project is a basic understanding of the biological and biochemical basis of Fv-1 restriction, a naturally occurring cellular system which inhibits the replication of specific N-or B-tropic mouse leukemia viruses. The studies primarily involve a variety of cell culture techniques for quantitation of virus replication and transformation. (1) MSV pseudotypes acquire sensitivity to Fv-1 restriction from murine leukemia virus during rescue and can be used as independent markers to detect restriction. Results show that infection of a resistant BALB/3T3 cell with at least 2 infectious N-tropic MuLV particles removes restriction to N-tropic MSV. The entire population of resistant cells can be made sensitive if sufficient N-tropic MuLV is added. (2) Mouse cells dually infected with N-tropic and B-tropic MuLVs yield progeny which are sensitive to both Fv-1b and Fv-1n restriction. The dual sensitivity is a phenotypic property of the virus and, together with the phenotypic acquisition of tropism by MSV psuedotypes, indicates that a transferable nongenetic factor, present in the leukemia or sarcoma virion, serves as a target for Fv-1 restriction, and that the restriction acts early in the viral replicative cycle.